US 12,404,553 B2
Biomarkers for bipolar disorder and schizophrenia
Terry W. Osborn, The Villages, FL (US); and Marquis Vawter, Laguna Niguel, CA (US)
Assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US); and LAGUNA DIAGNOSTICS, LLC, The Villages, FL (US)
Filed by THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US); and LAGUNA DIAGNOSTICS, LLC, The Villages, FL (US)
Filed on Jun. 12, 2023, as Appl. No. 18/333,231.
Application 18/333,231 is a continuation of application No. 16/333,626, granted, now 11,713,486, previously published as PCT/US2017/051716, filed on Sep. 15, 2017.
Claims priority of provisional application 62/395,159, filed on Sep. 15, 2016.
Prior Publication US 2023/0383354 A1, Nov. 30, 2023
Int. Cl. C12Q 1/6883 (2018.01); G01N 33/68 (2006.01)
CPC C12Q 1/6883 (2013.01) [G01N 33/6896 (2013.01); C12Q 2600/158 (2013.01); G01N 2800/302 (2013.01); G01N 2800/304 (2013.01); G01N 2800/60 (2013.01)] 14 Claims
 
1. A method of reducing the manifestation and/or progression of bipolar disorder (BD) and schizophrenia (SZ) in a human subject having BD or SZ comprising administering to the human subject one or more clinically approved antipsychotic drugs, wherein the human subject has been selected for administration of the one or more clinically approved antipsychotic drugs after completion of a 4-part gene expression assay on a sample of blood or cells from the human subject, wherein the human subject has been classified as having BD or SZ prior to the administration of the one or more antipsychotic drugs after (a) measuring the mRNA expression levels of each gene in the group consisting of SLC44A5, HADHA, CPA3, OXTR, CCDC109B, TREML4, TRIM4, PTGDS, HPR, EEF2, ZMYND8, TCEA3, IL5RA, GYLTL1B, FADS2, CRIP2, DDX5, and HLA-DRB5 in the sample and (b) correlating those measured levels with either BD or SZ by a logistic regression method comprising the following steps:
(i) first, the measured mRNA levels of each of the genes SLC44A5, HADHA, CPA3, OXTR, CCDC109B, TREML4, TRIM4, PTGDS, HPR, EEF2, and ZMYND8 are each multiplied by an associated weight factor and then added to form a weighted sum value; and the weighted sum value compared against a reference threshold, wherein a weighted sum value equal to or below this reference threshold identifies the subject as suspected of developing or having BD or SZ; then, second,
(ii) if the human subject is suspected of developing or having BD or SZ after step (i), the weighted sum value of the measured mRNA expression levels of each of the genes OXTR, PTGDS, FADS2, and HLA-DRB5 in the sample is calculated and compared against a reference threshold, wherein a weighted sum value equal to or below this reference threshold identifies the human subject as suspected of developing or having BD; and then, third,
(iii) if the human subject is suspected of developing or having BD or SZ after step (i), the weighted sum value of the measured mRNA expression levels of the genes TCEA3, SLC44A5, IL5RA, GYLTL1B, and DDX5 in the sample is calculated and compared against a reference threshold, wherein a weighted sum value equal to or below this reference threshold identifies the human subject as suspected of developing or having SZ; and then, fourth,
(iv(a)) if the human subject has been identified as suspected of developing or having BD after steps (i) and (ii), the weighted sum value of the measured mRNA expression levels of the genes OXTR, FADS2, and CRIP2 in the sample is calculated and compared against a reference threshold, wherein a weighted sum value above this reference threshold differentiates and classifies the human subject as having BD and not SZ; and
(iv(b)) if the human subject has been identified as suspected of developing or having SZ after steps (i) and (iii), the weighted sum value of the measured mRNA expression levels of the genes OXTR, FADS2, and CRIP2 in the sample is calculated and compared against a reference threshold, wherein a weighted sum value equal to or below this reference threshold differentiates and classifies the human subject as having SZ and not BD;
wherein the multiplication of mRNA levels by associated weight factors, the weighted sum values, and the reference thresholds are parts of the logistic regression method.